DESCRIPTION In many invertebrate and vertebrate species serotonin plays a relatively conserved neuromodulatory role, affecting motor output and the probability of performing different behaviors. In humans, serotonin has been strongly associated with depression. Yet, there is no clear idea of how it achieves its behavioral effects nor what is the natural input to the serotonergic system. A comprehensive description of the natural pathway through which the serotonergic system is activated could shed light on its physiological action. In the leech the serotonergic system is composed of a few types of neurons readily accessible to electrophysiological study. The major source of serotonin in this system, the Retzius (Rz) neurons, receive strong excitatory input from the pressure mechanosensory (P) neurons. The P-Rz connection is a polysynaptic pathway which spans the entire nerve cord and allows to channel mechanosensory input from any site of the body into a wide serotonergic output. The collaborators will investigate the organization of the neuronal pathway that mediates the P to Rz interaction. Their goal is to give a full description of the neurons that participate in this pathway. This will allow them to analyze how the sensory input channel produces fast behavioral responses, and at the same time activates modulatory pathways that change the behavioral responsiveness of the organism.